title: AR isoform 2 is widely expressed in human tissues and acts as a decoy receptor to regulate AR transcriptional activity

status: Public on Jun 29 2021

city: Bethesda

first: Kory

last: Johnson

state: MD

address: 10/3B01, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

summary: Together with the Estrogen, Progesterone, and Glucocorticoid Receptors, the Androgen Receptor (AR) is a member of the type I nuclear receptor superfamily, a class of transcription factors that are activated by steroid hormones1. Nuclear receptors share a common three-domain structure, comprising a highly variable amino-terminal domain (NTD), with potent transcriptional activator capability, a central two zinc finger motifs DNA-binding domain (DBD), and a well-conserved carboxy-terminal ligand-binding domain (LBD) responsible for interacting with the transcriptional machinery1. Given their modular structure, expression of isoforms resulting from alternative splicing or starting and termination events have profound effects on nuclear receptor activity and function. Several AR variants (AR-Vs) have been identified from prostate cancer clinical specimens, arising from multiple mechanisms, including genomic rearrangements2 and upregulation of splicing factors3. This seminal discovery has provided the molecular basis for a deeper understanding of AR-related diseases, with potential to be translated in identification of novel therapeutic targets and promising prognostic markers4–6. By deeply sequencing the transcriptome of human brains, here we identified AR-2 as the most expressed AR isoform. Furthermore, we found that AR-2 is widely expressed in other human tissues, forms heterodimers with the full length AR and acts as a repressor of its transcriptional activity. Delivery of this isoform via adeno-associated virus (AAV9) resulted in significant amelioration of the disease phenotype in a mouse model of spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease with unmet clinical need caused by a toxic gain of function of polyglutamine-expanded (polyQ) AR7. Collectively, these results establish a physiological role of AR-2 in fine-tuning full length AR activity and demonstrate the feasibility and therapeutic benefit of modulating this variant for treating SBMA and other AR-related diseases.

overall_design:
RNA sequencing was performed on a total of 26 human samples. Of these samples, three represented three different brain regions for one SBMA patient, five represented three different brain regions for two neurological controls, six represented three different brain regions for two non-neurological controls, six represented iPSC-derived motor neurons from three different SBMA patients cultured under EtOH or DHT condition, and six represented iPSC-derived motor neurons from three controls cultured under EtOH or DHT condition.

Neurological controls = brain samples from patient(s) that have a diagnosed neurological disease/disorder other than SBMA

NonNeurological_Controls = brain samples from patients that do not have a diagnosed neurological disease/disorder, but rather represent brain with non-disease/non-disorder neurological deficits associated with age.

first: Wooi

last: Lim

first: Jesse

last: Dabney

first: Mitra

last: Forouhan

first: Ruth

last: Ellerington

first: Alfina

last: Speciale

first: Raquel

last: Manzano

first: Maria

last: Lieto

first: Gavinda

last: Sangha

first: Subhashis

last: Banerjee

first: Mariana

last: Conceicao

first: Lara

last: Cravo

first: Miguel

last: Lobo

first: Annabelle

last: Biscans

first: Loïc

last: Roux

first: Naemeh

last: Pourshafie

first: Christopher

last: Grunseich

first: Stephanie

last: Duguez

first: Anastasia

last: Khvorova

last: Pennuto

first: Costanza

last: Cortes

first: Albert

last: La Spada

first: Kenneth

middle: H

last: Fischbeck

first: Matthew

last: Wood

first: Carlo

last: Rinaldi


title: Epic methylation arrays of DNMT1 inhibitor treated AML cell lines

status: Public on Jun 30 2021

city: Collegeville

first: Shawn

middle: W

last: Foley

state: PA

address: 1250 S. Collegeville Rd

department: Oncology

country: USA

institute: GlaxoSmithKline

summary: Genome wide demethylation by DNMT1 inhibitor GSK3685032 results in up-regulation of epigenetically-silenced genes

overall_design: Methylation was assayed for each cell line following DNMT1 inhibitor or vehicle treatment across 6 point dose titration and 6 day timecourse. Global methylation distributions were compared across the dose and timecourse.

first: Melissa

middle: B

last: Pappalardi

first: Michael

middle: T

last: McCabe

first: Wendy

middle: A

last: Kellner

first: Kathryn

last: Keenan


title: MethylationEPIC array of DNMT1 inhibitor treated AML cell lines - part II

summary: Genome wide demethylation by DNMT1 inhibitor GSK3484862 results in up-regulation of epigenetically-silenced genes. Methylation was assayed for each cell line following DNMT1 inhibitor or vehicle treatment. Global methylation distributions were compared between treated and untreated samples.

overall_design: Seven AML cell lines were treated for 96 hours in biological duplicate with 0.1% DMSO or 1 µM GSK3484862 before isolating gDNA, labeling, and hybridizing to MethylationEPIC arrays.


title: Transcriptomic study of the HT22 cells after OGD treatment.

status: Public on Jun 28 2021

city: Luzhou city

first: Qiancheng

last: Mu

state: Sichuan Province

address: Taiping Street, 25

department: Department of Neurosurgery

country: China

institute: the Affiliated Hospital of Southwest Medical University

type: Expression profiling by high throughput sequencing

summary: To investigate the key genes of ischemic stroke, the oxygen glucose deprivation model and RNA sequence of HT22 neuronal cells were performed. By comparing with each other, we identified 51 up-regulated and 119 down-regulated genes in 3H vs 0H, 229 up-regulated and 50 down-regulated genes in 6H-vs-3H, and 145 up-regulated and 121 down-regulated genes in 6H-vs-0H. The results indicate that c-Fos acts as the most key gene at 51 up-regulated genes in 3H vs 0H.

overall_design: RNA-seq of HT22 cells after OGD treatment.

first: Yuxuan

last: Zhang

first: Long

last: Gu


title: Real-time quantitative PCR analysis of human renal biopsies

status: Public on Jul 09 2021

city: Dijon

first: Baptiste

last: Lamarthée

address: Bd du Mal De Lattre de Tassigny

department: RIGHT

country: France

institute: Inserm U1098

summary: Human biopsies were collected from kidney transplant recipients in 4 different european centers in the context of BIOMARGIN study. We used TaqMan™ Advanced miRNA Human A and B Cards to quantitate 754 miRNAs expression according to patient outcome ; ie patient presenting Microvascular Inflammation  (MVI) or No MVI .

overall_design: qPCR MiRNA expression profiling. Needle core biopsies from 88 kidney transplant recipients were collected  and immediatly stored in Allportect Tissue Reagent at -20°C before RNA extraction. Equal amount of total RNA (150 ng) from each patient was used to gene expression analysis.

first: Claire

last: Tinel

first: Virginia

last: Sauvaget


title: Temporal controls over interareal cortical projection neuron fate diversity (connectID)

status: Public on Jul 01 2021

city: Geneva

first: Julien

last: Prados

address: Rue Michel Servet 1

department: SCMU

country: Switzerland

institute: University of Geneva

summary: Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.

overall_design: This record contains single cell transcriptomics data from 7 Fluidigm integrated fluidic circuits and 66 bulk RNA-seq from the same 11 mouse cortex. A 32bp-barcoded sindbis virus is injected in the primary somatosensory cortex of P14, P9 and P7 pups. The virus enter the neurons, replicate and migrate to the terminal connections. Then, S1 cells are FACS-sorted and their transcriptome is sequenced using Fluidigm integrated fluidic circuits on C1 system. In addition, 6 projection targets where S1 cells are expected to project are dissected and barcodes of the Sindbis viruses are sequenced by bulk RNA-seq. This allow to link the transcriptome of S1-cells to their projection targets.

first: Esther

last: Klingler

first: Ugo

last: Tomasello

first: Justus

last: Kebschull

first: Alessandro

last: Contestabile

first: Gregorio

last: Galiñanes

first: Sabine

last: Fièvre

first: Daniel

last: Huber

first: Alexandre

last: Dayer

first: Camilla

last: Bellone

first: Antonio

last: Santinha

first: Randall

last: Platt

first: Denis

last: Jabaudon


title: Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury [rat]

status: Public on Jul 06 2021

city: Seoul

first: Soo-Jong

last: Hong

state: Seoul

address: Department of Medicine, 88, OLYMPIC-RO 43-GIL, SONGPA-GU

country: South Korea

institute: University of Ulsan Collage of Medicine

summary: Inhalation of toxic chemicals, including recent e-cigarettes, often cause life-threatening lung injury. Although exposure to polyhexamethylene guanidine (PHMG)-containing humidifier disinfectant (HD) has been identified as a cause of fatal lung injury, the mechanism underlying HD-associated lung injury (HDLI) is unknown. The present study evaluated global changes in gene expression in lung tissues from patients with PHMG-induced HDLI, and compared gene expression changes in PHMG-induced rat lung tissues. Significantly different expressions in lung tissues between patients with HDLI and unaffected controls were observed. Furthermore, several fibrosis-associated overlapping genes (such as MMP2 and COL1A2) shared between humans with HDLI and rats exposed to PHMG were identified. Interactome network analysis predicted different pathways between children and adults with HDLI: the TGFβ/SMAD signaling pathway was central in adults, whereas other pathways, including integrin signaling, were associated with HDLI in children. Further interactome network analysis revealed that Rap1 and CCKR signaling pathways were significantly enriched in HDLI compared with idiopathic pulmonary fibrosis as well as their recapitulation in the lung tissues of rats exposed to PHMG. Our results suggest that MMP2-mediated different mechanisms between children and adults may be associated with PHMG-induced HDLI development, and Rap1 and CCKR pathways appear to be crucial.

overall_design: (frozen rat lung tissues from 10 PHMG-exposed rats and 10 non-exposed controls

first: Jeong-Hyun

last: Kim

first: Kwoneel

first: Jeonghun

last: Yeom

first: Eun

last: Lee

first: Mi-Jin

last: Kang

first: Seung-Hwa

first: Kyunggon

first: So-Yeon

first: Sang-Bum

first: Dong

middle: K

last: Oh

first: Kyuhong

first: Seong-Jin

last: Choi

last: Yang


title: Intra-ocular dendritic cells characterize HLA-B27-associated acute anterior uveitis

status: Public on Jun 25 2021

city: Muenster

first: Michael

last: Heming

address: Albert-Schweitzer-Campus 1, Bldg A1

department: Department of Neurology with Institute of Translational Neurology

country: Germany

institute: University Hospital Muenster

summary: Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations.  Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27 positive (n=3) and negative (n=2) anterior uveitis and an infectious endophthalmitis control (n=1) by combining single cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27 positive uveitis exclusively featured a plasmacytoid and classical dendritic cells (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication.  This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27 positive uveitis with relevance of dendritic cells.

overall_design: Single-cell RNA profiling of intraokular leukocytes from HLA-B27 positive (n=3) compared with HLA-B27 negative (n = 2)  anterior uveitis and an infectious endophthalmitis (n=1)

first: Maren

last: Kasper

first: Arnd

last: Heiligenhaus

first: Gerd

last: Meyer zu Hörste


title: TCF7L2 lncRNA: A Link between Bipolar Disorder and Body Mass Index through Glucocorticoid Signaling [RNA-Seq]

status: Public on Jul 21 2021

city: Rochester

first: Thanh Thanh

middle: Le

last: Nguyen

state: Minnesota

address: 200 1st St. SW

institute: Mayo Clinic

summary: Bipolar disorder (BD) and obesity are highly comorbid. We previously performed a genome-wide association study (GWAS) for BD risk accounting for the  effect of body mass index (BMI) which identified a genome-wide significant single-nucleotide polymorphism (SNP) in the gene encoding the transcription factor 7 like 2 (TCF7L2). However, the molecular function of TCF7L2 in the central nervous system (CNS) and its possible role in BD and BMI interaction remained unclear. In the present study, we demonstrated by studying human induced pluripotent stem cell (hiPSC)-derived astrocytes, cells which highly express TCF7L2 in the CNS, that the BD-BMI GWAS risk SNP is associated with glucocorticoid-dependent repression of the expression of a previously uncharacterized TCF7L2 transcript variant. That transcript is a long non-coding RNA (lncRNA-TCF7L2) that is highly expressed in the CNS but not in peripheral tissues such as the liver and pancreas which are involved in metabolism.  In astrocytes, knock-down of the lncRNA-TCF7L2 resulted in decreased expression of the parent gene, TCF7L2, as well as alterations in the expression of a series of genes involved in insulin signaling and diabetes.  We also studied the function of TCF7L2 in hiPSC-derived astrocytes by integrating RNA sequencing data after TCF7L2 knock-down with TCF7L2 chromatin-immunoprecipitation sequencing (ChIP-seq) data. Those studies showed that TCF7L2 directly regulated a series of BD-risk genes. In summary, these results support the existence of a CNS-based mechanism underlying BD-BMI genetic risk, a mechanism based on a glucocorticoid-dependent expression quantitative trait locus that regulates the expression of a novel TCF7L2 non-coding transcript.

overall_design: TCF7L2 was knocked-down (KD) in human iPSC-derived Astrocytes. Additionally, TCF7L2 lncRNA was KD in astrocytes. RNA-seq was then conducted to compare the transcriptomes of KD and wildtype conditions.

first: Duan

last: Liu

middle: L

first: Huanyao

last: Gao

first: Huaizhi

last: Huang

first: Daniel

first: Brenna

last: Sharp

first: Zhenqing

last: Ye

first: Jeong-Heon

first: Brandon

last: Coombes

first: Tamas

last: Ordog

first: Liewei

last: Wang

first: Joanna

last: Biernacka

first: Mark

last: Frye

first: Richard

middle: M

last: Weinshilboum


title: RNA-seq of murine lung mesenchymal stromal cells (LMSCs) during tumor progress

status: Public on Jul 03 2021

city: suzhou

first: Zhiyuan

last: Zheng

address: 199,Ren ai Road

institute: Soochow University

summary: Purpose: The goals of this study are to explore the function of  lung MSCs during tumor development. Methods: mRNA profiles of lung MSCs (murine) were generated by deep sequencing.

overall_design: RNA-seq of 3 different stge MSCs during tumor progress: adenoma (A-LMSC),  pre-metastatic (PM-LMSC) and metastatic stage (M-LMSC).n=1

first: Yufang

last: Shi


title: RNA-Seq analysis of WT and BbWor1 disruption strain in beauveria bassiana

city: Ji nan

first: zhang

middle: tong

last: sheng

address: 3501 Daxue Road, Changqing District,

institute: Qilu University of Technology

summary: Wor1 is a conserved fungal regulatory protein that control the phenotypic switching and pathogenicity of Candida albicans.We simulated three models of Beauveria bassiana morphological transitions, including CTH (conidia to hyphae), HTC (hyphae to conidia) and BTB (blastospore to blastospore).We find that disruption of BbWor1 (an ortholog of Wor1) resulted in a distinct reduction in the time required for germination (CTH), a significant increase in hyphal growth and a decrease in the yield of conidia (HTC), indicating that BbWor1 positively controls conidia production and negatively regulates hyphal growth in conidia-hyphae switching. Meanwhile, the ΔBbWor1 prominently decreased blastospore yield, as well as shortening G0/G1 phase and prolonging G2/M phase, under the BTB model. Importantly, BbWor1 contributed to conidia-hyphae switching and blastospore propagation via different genetic pathways, and yeast one-hybrid testing demonstrated the necessity of BbWor1 to control the transcription of an allergen-like protein gene (BBA_02580), as well as a conidial wall protein gene (BBA_09998). Moreover, the dramatically weakened virulence of ΔBbWor1 was examined by immersion and injection methods.

overall_design: Transcriptome comparison of wild type (WT) and  BbWor1 disruption type in Beauveria bassiana under three models

first: Lei

last: Qiu

first: Tong-Sheng

last: Zhang

first: Ji-Zheng

last: Song

first: Jing

first: Ze

last: Li

first: Juan-Juan


title: Next Generation Sequencing (m6A-seq) Reveals RNA m6A Methylation Patterns During the Expansion of Tomato

city: Xuzhou

first: Tao

last: Xu

state: Jiangsu

address: Shanghai Road 101

institute: Jiangsu Normal University

type: Methylation profiling by high throughput sequencing

summary: In this study, we show the potential link between m6A deposition and fruit expansion in tomato (Micro-tom). m6A level was increased during fruit expansion. Later, a parallel analysis of the m6A -seq and RNA-seq in expanding fruit were preformed to evaluate global correlation between m6A modification and fruit expansion. Our m6A -seq reveal that thousands of protein-coding genes contains m6A modification with a consensus motif and primarily enriched in the 3’untranslated regions. Gene ontology analysis indicate that the distribution of m6A in expanded fruit is largely associated with plant-specific processes relating to the chloroplast function. Moreover, we further uncover a positive correlation between m6A methylation and the mRNA abundance. Specifically, large number of fruit expansion-related genes, which involved in hormone and endoreplication, were m6A modified and actively expressed compared to non- m6A modified genes, suggesting a potential involvement of m6A modification in fruit expansion. Collectively, our result suggests a dynamic role of m6A modification involving in fruit expansion.

overall_design: The MicroTom fruit samples were collected at 12, 20, 28 day after flowering. And the RNA extracted from fruit samples with two biological replicates was subjected to m6A and RNA sequencing.For data analysis,the early fruit sample at 12 day after folwering was used as reference sample to investigate the role of m6A in fruit expansion process.

first: Hunseung

last: Kang


title: Identification of differentially expressed miRNAs in exosomes secreted from human colon cancer stem cells.

city: Taichung

first: Wei-Chung

last: Cheng

address: No.91, Hsueh-Shih Road

country: Taiwan

institute: China Medical University

type: Non-coding RNA profiling by high throughput sequencing

summary: As accumulating evidence suggests cancer cells exhibit stem-like properties for advanced diseases and cancer stem cells (CSCs) have been identified in various tumor types, revisiting present knowledge toward CSCs is essential.  The identification of exosome-loaded miRNAs responsible for stemness and chemoradioresistance of CSCs should eventually leadd to development of novel therapeutic approaches.

overall_design: Expression profiles of miRNAs of purified exosomes from parental HCT15/29 cells and HCT15/29-derived cancer spheres were generated for identifying central miRNAs for CSC malignancy.

first: Wei-Lun

last: Hwang


title: Changes in chromatin accessibility over time in cells expressing t(4;11) fusion proteins [I]

status: Public on Jun 22 2021

city: Frankfurt am Main

first: Lukas

last: Jost

address: Altenhöferallee 3

institute: GenXPro GmbH

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We have used a constitutive MLL-AF4 fusion gene together with a inducible AF4-MLL fusion gene to investigate the power of theses fusion proteins. All transgenes were stably or transiently transfected.

overall_design: Fusion genes were constructed by fusing distinct cDNA portions of MLL/KMT2A with corresponding AF4 fragment.

first: Rolf

last: Marschalek


title: Heterozygous  OAS1 Gain-of-Function Variants Cause a Polymorphic Autoinflammatory and Immunodeficiency Syndrome

status: Public on Jun 18 2021

city: München

first: Thomas

last: Magg

address: Lindwurmstr. 2a

institute: Dr. von Haunersches Kinderspital der LMU München

summary: Oligoadenylate synthase 1 (OAS1) is a type-1 interferon-inducible, intracellular double-stranded RNA (dsRNA) sensor that generates 2'-5'-oligoadenylate (2-5A) to activate RNaseL as a means of antiviral defense. We report four de novo heterozygous OAS1 variants in five patients. Variant OAS1 proteins show dsRNA-independent gain-of-function 2-5A synthetase activity that results in RNaseL-mediated RNA-cleavage, transcriptomic downregulation, and functional impairment and/or apoptosis of monocytes, iPSC-derived macrophages, and B-cells. This leads to a polymorphic syndrome of monocyte, macrophage, and B-cell deficiency characterized by autoinflammation, pulmonary alveolar proteinosis, and hypogammaglobulinemia. RNase-L-inhibition in vitro mitigates, and hematopoietic cell transplantation in vivo corrects the autoinflammatory and immunodeficiency phenotype.

overall_design:
iPSC-derived macrophages, poly-A tailed mRNA isolation, library preparation and quantification were performed with NEBNext kits (New England Biolabs, Ipswich, USA) following manufacture’s instructions. Libraries were sequenced on a NextSeq 500 (Illumina, San Diego, USA)

Poly-A selection?based RNA sequencing (RNA-seq) was performed on FACS-sorted OAS1-WT (three different healthy donors (HD), HD1 and HD2 in duplicates) and A76V (in duplicates) CD14 monocytes, CD19 B cells, and CD3 T cells. Libraries were sequenced on a single lane in 100 bp single end mode on a HiSeq1500 instrument (Illumina, San Diego, USA).

first: T

last: Okano

first: L

last: Koenig

first: D

middle: R

last: Boehmer

first: S

last: Schwartz

first: K

last: Inoue

first: J

last: Heimall

first: F

last: Licciardi

last: Ley-Zaporozhan

first: R

last: Ferdman

first: A

last: Caballero-Oteyza

first: E

middle: N

last: Park

first: B

last: Calderon

last: Dey

first: H

last: Kanegane

last: Cho

last: Montin

last: Reiter

first: M

last: Griese

last: Albert

last: Rohlfs

first: P

last: Gray

first: C

last: Walz

first: G

last: Conn

middle: E

last: Sullivan

last: Klein

last: Morio

last: Hauck


title: RNA-seq of DNMT1 inhibitor treated AML cell lines

first: Shawn

last: Foley

summary: Genome wide demethylation by DNMT1 inhibitors GSK3685032 results in up-regulation of epigenetically-silenced genes.

overall_design: Differential expression was perfomed for each cell line following DNMT1 inhibitor or vehicle treatment across 6 point dose titration and 6 day timecourse. Differentially epressed gene lists were compared across the dose and timecourse.

first: Melissa

last: Pappalardi

first: Michael

last: McCabe

first: Wendy

last: Kellner

first: Kathryn

last: Keenan


title: Transcriptome analysis of WWC2-deficient E11.5 embryos

city: Münster

first: Anke

last: Hermann

address: Albert-Schweitzer-Campus 1

department: Internal Medicine D

institute: University Hospital Münster

summary: The Hippo signaling pathway is known to regulate cell differentiation, proliferation and apoptosis. The WWC proteins, WWC1 and WWC2, positively regulate the Hippo pathway by the activation of the LATS kinases and the subsequent cytoplasmic translocation of YAP. The in vivo role of WWC2 has not been studied, yet. We could show, that the ubiquitous knockout of WWC2 in mice leads to placental defects, growth retardation, a disturbed angiogenesis and vascularization resulting in embryonic lethality at around E11.5. To further understand the function of WWC2 in the embryonic development, a transcriptome analysis by next generation sequencing was performed.

overall_design: The gene expression of 4 samples of E11.5 embryos homozygous for the WWC2 deletion were compared to 3 samples of E11.5 embryos heterozygous for the WWC2 deletion and 3 samples of wildtype embryos

first: Joachim

last: Kremerskothen


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis [HiC]

city: Goettingen

first: Argyris

last: Papantonis

address: Robert-Koch-Str 40

department: Department of Pathology

institute: University Medical Center Goettingen

summary: Mammalian chromosomes are three-dimensional entities shaped by converging and opposing forces acting on chromatin. Mitotic cell division induces drastic chromatin condensation, but following reentry into the G1 cell cycle phase, condensed chromosomes unwind to re-establish interphase organization. Here, we use a cell line allowing auxin-mediated degradation of RNA polymerase II to test its role in this transition. In situ Hi-C and super-resolution imaging showed that RNAPII is required for compartment and loop formation following mitosis. RNAPs also often counteract loop extrusion and, in their absence, longer and more prominent loops arise. Evidence from chromatin fractionation and in silico modeling attribute these effects to RNAPII-mediated cohesin loading at active promoters upon G1 reentry. Our findings reconcile the role of RNAPII in gene expression with that in chromatin architecture.

overall_design: HiC sequencing in DLD1 cells

first: Nadine

last: Übelmesser

first: Shu

last: Zhang


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Changes of transcriptome in endothelial cells from kidney with tubule-specific conditional Vhlh gene knockout (Hoxb7-Cre-GFP; VhlhloxP/loxP), compared with wild-type.

first: Tien

last: Hsu

department: Graduate Institute of Biomedical Sciences

summary: Clear-cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of RCC in which more than 80% of ccRCC cases are associated with early inactivation of von Hippel-Lindau (VHL) tumor suppressor gene. We have generated a knockout mouse strain in which mouse allele of VHL (Vhlh) is conditionally deleted in the kidney epithelium (cortical tubules, collecting ducts and ascending Loops of Henle). These knockout mice showed high penetrance of inflammation and fibrosis in the kidney in addition to hyperplasia and the appearance of transformed clear cells. These results support the concept of tumor-promoting inflammation. Surprisingly, we found that the expression of pJNK, a marker of inflammation, was expressed in endothelial cells (ECs) in Vhlh mutant tissue although the knockout was in epithelial cells not in endothelial cells. The result indicated the important role of ECs in the initiation tumor progression. Therefore, the aim of this study is to investigate the molecular changes of ECs in the VHL mutant microenvironment.

overall_design: ECs from kidney of 3-month old male mice of mutant (Hoxb7-Cre-GFP-VhlhloxP/loxP, named ECs-KO) and control wildtype (Hoxb7-Cre-GFP, named ECs-WT) were isolated by anti-Cd31 antibody-conjugated magnetic beads. Total mRNAs of these isolated ECs were extracted immediately without additional culturing to capture as close as possible the in vivo molecular profile of ECs.

first: Hieu-Huy

last: Nguyen-Tran


title: RNA Biological Characteristics at the Peak of Cell Death in Different Hereditary Retinal Degeneration Mutants

status: Public on Jun 26 2021

city: Kunming

first: kangwei

last: Jiao

state: Yunnan

address: 176 Qingnian

department: Ophthalmology

institute: Yunnan University

summary:
Purpose: The present work investigated changes in the gene expression, molecular mechanisms, and pathogenesis of inherited retinal degeneration (RD) in three different disease models to identify predictive biomarkers for their varied phenotypes and to provide a better scientific basis for their diagnosis, treatment, and prevention.
Methods: Differentially expressed genes (DEGs) between retinal tissue from RD mouse models obtained during the photoreceptor cell death peak period (Pde6brd1 at post-natal (PN) day 13, Pde6brd10 at PN23, Prphrd2 at PN29) and retinal tissue from C3H wild-type mice were identified using Illumina high-throughput RNA-sequencing. Co-expression gene modules were identified using a combination of GO and KEGG enrichment analyses and gene co-expression network analysis. CircRNA-miRNA-mRNA network interactions were studied by genome-wide circRNA screening.
Results: Pde6brd1, Pde6brd10, and Prphrd2 mice had 1,926, 3,096, and 375 DEGs, respectively. Genes related to ion channels, stress, inflammatory processes, tumor necrosis factor (TNF) production, and microglial cell activation were up-regulated, while genes related to endoplasmic reticulum regulation, metabolism, and homeostasis were down-regulated. Differential expression of transcription factors and non-coding RNAs generally implicated in other human diseases was detected (e.g Gloucoma, diabetes retinopathy and inherited retinal degeneration). CircRNA-miRNA-mRNA network analysis indicated that these factors may be involved in photoreceptor cell death. Moreover, excessive cGMP accumulation causes photoreceptor cell death, and cGMP-related genes were generally affected by different pathogenic gene mutations.
Conclusions: We screened genes and pathways related to photoreceptor cell death. Additionally, up-stream regulatory factors, such as transcription factors and non-coding RNA and their interaction networks were analyzed. Furthermore, RNAs involved in RDs were functionally annotated. Overall, this study lays a foundation for future studies on photoreceptor cell death mechanisms.

overall_design: Retinal mRNA profiles RD mouse models obtained during the photoreceptor cell death peak,(Pde6brd1 at post-natal (PN) day 13, Pde6brd10 at PN23, Prphrd2 at PN29) and retinal tissue from C3H wild-type mice were identified using Illumina high-throughput RNA-sequencing.

first: Kangwei

first: Chunling

last: Wei

first: Yan

last: Li

first: Xiaoxiao

last: Feng

first: Zhulin

last: Hu

first: François

last: Paquet-Durand


title: Expression profile and potential function of circRNAs in peripheral blood mononuclear cells from patients with primary gout

city: Nanchong City

first: daifei

last: dai

address: No. 234, Fujiang Road, Shunqing District

institute: North Sichuan Medical College

summary: To determine the expression profile and clinical significance of circular RNAs (circRNAs)  in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human circRNA microarrays were used to identify the differentially expressed circRNAs in primary gout (Gout, n = 5) and healthy subjects (HC, n = 3). Bioinformatics analyses were performed to predict the roles of differently expressed circRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results in 90 gout patients, and 60 healthy control subjects (HC). Microarray analysis indicated that 238 circRNAs were up-regulated and 41 circRNAs were down-regulated in the Gout group (Fold change>1.5, p-value<0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout through a variety of different pathways. Significant association was observed between these circRNAs and lipid metabolism indicators. Our results provide novel insight into the mechanisms of primary gout, and reveal that  hsa_circRNA_103657 could effectively discriminate the gout group and the healthy control groups.

overall_design: Two-condition experiment：primary gout patients vs. healthy control subjects peripheral blood mononuclear cells. Biological replicates: 5 gout patients replicates，3 controls replicates.

first: Fei

last: Dai

first: Quan-Bo

first: Yi-Ping

last: Tang

first: Yi-Xi

last: He

first: Ting

last: Yi

first: Yu-Feng

last: Qing


title: B cell residency but not T cell-independent IgA switching in the gut requires innate lymphoid cells

city: Morgantown

first: Gangqing

state: West Virginia

address: 64 Medical Center Drive

department: MicroBiology, Immunology, and Cell Biology

institute: West Virginia University

summary: Immunoglobulin A (IgA)-producing plasma cells derived from conventional B cells in the gut play an important role in maintaining the homeostasis of gut flora. Both T cell-dependent and T cell-independent IgA class switching occurs in the lymphoid structures in the gut, whose formation depends on lymphoid tissue inducers (LTis), a subset of innate lymphoid cells (ILCs). However, our knowledge on the functions of ILCs, the innate counter parts of CD4 T helper cells, in promoting IgA production is still limited. By cell adoptive transfer and utilizing a unique mouse strain, we demonstrated that the generation of IgA-producing plasma cells from B cells in the gut occurred efficiently in the absence of both T cells and ILCs and without engaging TGFβ signaling. Nevertheless, B cell recruitment and/or retention in the gut required NKp46-CCR6+ LTis. Therefore, while ILCs contribute to the accumulation of B cells in the gut through inducing lymphoid structure formation, they are not essential for the T cell-independent generation of IgA-producing plasma cells.

overall_design: Live Lin-CD127+ KLRG1-NK1.1-NKp46-CCR6+ lymphoid tissue inducer (LTi) cells from small intestine lamina propria (siLP) of Gata3+/+ and Gata3fl/flVavCre mice were used for RNA-Seq analysis.

first: Mingzhu

last: Zheng

first: Kairui

last: Mao

first: Difeng

last: Fang

first: Dan

first: Jun

last: Lyu

first: Dingkang

last: Peng

first: Xi

last: Chen

first: Nikki

last: Cannon

first: Jiajia

last: Han

first: Keji

last: Zhao

first: Wanjun

first: Jinfang

last: Zhu


title: Disruption of Y chromosome expression in male lung cancer: replication

status: Public on Jun 15 2021

city: London

first: William

last: Cookson

address: Dovehouse Street

country: United Kingdom

institute: Imperial College London

summary: Lung cancer is the single most frequent cause of cancer death worldwide and is relatively more common in males. For reasons that are currently unknown, lung cancer is also associated with significantly worse outcomes in men than women. Here we replicate clustering of Y-chromosome transcripts identified previously as showing tumor-specific disruption in men with lung cancer.

overall_design: Human whole transcriptome data were generated from pulmonary tumor and, where possible, matched unaffected tissue (referred to hereon as ‘normal’) using the Affymetrix HuGene 1.1 ST microarray, giving a total of 123 samples from 69 patients. Tumor samples and adjacent normal lung tissue were donated from surgical resections, undertaken with curative intent.

first: Madeleine

last: Arseneault

middle: C

first: Clara

last: Domingo Sabugo

first: Maxim

last: Freidin

first: Shir

last: Kiong Lu

first: Mark

last: Lathrop

first: Liming

last: Liang

first: Eric

last: Lim

first: Miriam

middle: F

last: Moffatt

first: Andrew

middle: G

last: Nicholson

first: Sanjay

last: Popat

first: Yasser

last: Riazalhosseini

first: Elizabeth

last: Starren

first: Saffron

last: Willis-Owen

first: Youming

last: Zhang


title: Global transcriptional profiling of HCC827 lung adenocarcinoma cells in response to EGFR inhibition

status: Public on Jun 24 2021

city: La Jolla

first: Jorge

middle: Silvio

last: Gutkind

state: CALIFORNIA

address: 3855 Health Sciences Drive

department: Moores Cancer Center

institute: UC San Diego

summary: mRNA sequencing of EGFR mutant HCC827 lung adenocarcinoma cells were treated with erlotinib (EGFR inhibitor) for 24hr to profile and characterize dysregulated pathways in response to EGFR inhibition

overall_design: HCC827 cells treated with 24h erlotinib or DMSO control in a 3 vs 3 sample design

first: J

middle: S

first: Nadia

last: Arang

first: Toshinori

last: Ando


title: Changes in chromatin accessibility over time in cells expressing t(4;11) fusion proteins

first: Lukas

last: Jost


title: Disruption of Y chromosome expression in male lung cancer

first: William

last: Cookson


title: Comparative methylation and RNAseq expression analysis on CpG context to identify genes involved in backfat vs liver diversification in Nanchukmacdon pig

status: Public on Jun 08 2021

city: Jeonju

first: Devender

last: Arora

address: 1500, Kongjwipatjwi-Ro, Iseo-Myeon, Wanju-gun

institute: NIAS

summary: We report the significant role methylation in differentially expressed genes in backfat and liver tissue of Nanchukmacdon pig

overall_design: Examination of Liver and Backfat tissue

first: Woncheoul

last: Park


title: Disruption of Y chromosome expression in male lung cancer: discovery

summary: Lung cancer is the single most frequent cause of cancer death worldwide and is relatively more common in males. For reasons that are currently unknown, lung cancer is also associated with significantly worse outcomes in men than women. Here we examine the pulmonary transcriptome in lung cancer at a systems level through network analysis. We compare gene expression networks in affected and unaffected tissue derived from 126 patients with lung cancer. Examination of tissue-specific co-expression patterns reveals markedly poor preservation of a sex-associated gene co-expression network in tumor tissue.

overall_design: Human whole transcriptome data were generated from pulmonary tumor and, where possible, matched unaffected tissue (referred to hereon as ‘normal’) using the Affymetrix HuGene 1.1 ST microarray, giving a total of 237 samples from 126 patients. Tumor samples and adjacent normal lung tissue were donated from surgical resections, undertaken with curative intent.

first: Madeleine

last: Arseneault

middle: O

first: Clara

last: Domingo Sabugo

first: Maxim

last: Freidin

first: Shir

last: Kiong Lu

first: Mark

last: Lathrop

first: Liming


title: Circular RNA Expression Profiles during white adipogenesis

status: Public on Jun 21 2021

city: Xinyang

first: pengpeng

state: Henan

address: No.237 Nanhu Road Shihe District

institute: Xinayang Normal University

summary: The aims of the current study were to characterize the profile of circRNA during WATadipocytes adipogenesis.

overall_design: Primary WATpreadipocyte were isolated, and induced to adipogenic differentiation. The samples were collected on Day 0, Day 4 and day 8 post differentiation

first: Pengpeng

first: Yongjie

last: Xu

first: Haixia

first: Cencen

last: Li


title: Changes in chromatin accessibility over time in cells expressing t(4;11) fusion proteins [II]

summary: We have used a combination of constitutive and inducible MLL-AF4 and AF4-MLL fusion genes to investigate the power of theses fusion proteins. All transgenes were stably or transiently transfected. Here, we compared 48 induction of MLL-AF4 or AF4-MLL (day 3) and looked for persistance at days 28. This was compared to the situation with constitutive MLL-AF4 with 48 inductionn of AF4-MLL at day 3 and day 28.

first: Rolf

last: Marschalek


title: Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy

status: Public on Jun 03 2021

city: Boston

first: Marie

last: Siwicki

state: MA

address: Simches Research Building, 185 Cambridge Street

department: Center for Systems Biology

institute: Harvard / MGH

summary: Immunotherapy is revolutionizing cancer treatment but can trigger toxicities that remain poorly understood. Here, by comprehensively analyzing mouse models following anti-CD40 therapy, we found an interdependent induction of the cytokines IFN-g and IL-12, which caused inflammatory pathology in various tumor-free tissues. In the liver, Kupffer cells mediated toxicity by sensing lymphocyte-derived IFN-g and producing IL-12, highlighting the vulnerability of tissue-resident macrophages to promote toxicity when reacting to proinflammatory cues. Conversely, dendritic cells drove tumor control but were dispensable for toxicity. We further show that liver macrophages, IL-12, and IFN-g were not toxic themselves, but prompted a neutrophil response that determined the severity of tissue damage. Similar inflammatory pathways characterized immunotherapy-related adverse events in cancer patients. These findings implicate resident macrophages and neutrophils as mediators and effectors of aberrant inflammation, and suggest distinct cellular mechanisms of toxicity and antitumor immunity.

overall_design: Bulk RNAseq of neutrophils either sufficient or deficient for IFNgR1, isolated from the livers of MC38 tumor-bearing mice treated with anti-CD40 agonist immunotherapy. Mice were 50:50 bone marrow chimeras harboring both wild type and Ifngr1-/- immune cells. Each mouse (2-9) yielded samples n.1 (wild type) and n.2 (Ifngr1-/-).


title: A humanized mouse strain that develops spontaneously immune-mediated diabetes.

status: Public on Jun 02 2021

city: Paris

first: Franck

last: Letourneur

address: 22 rue mechain

institute: INSERM

summary:
The clinical management of type 1 diabetes (T1D) faces the lack of fully predictive biomarkers and of antigen-specific therapies to prevent its development. From a therapeutic standpoint, preclinical modls of T1D have fallen short of directly translating into the human.
To circumvent this limitation, we developed a new mouse model that is deficient for expression of murine major histocompatibility complex class I, class II and of murine insulin genes and instead expresses HLA-A*02:01, the high susceptibility HLA-DQ8 molecule and human insulin.
The metabolic and immune phenotype of these mice is basically identical to that of the parental strains. Upon expression of B7.1 under the control of the rat insulin promoter, these mice develop T1D along with a T-lymphocyte response to human preproinsulin epitopes spanning the whole autoantigen sequence.
This new model will allow evaluating peptide-based immunotherapy that may directly apply to human T1D.

overall_design: We analysed 5 YES-RIP-hB7.1 mice to compare with YES mouse, NOD mouse and C57BL/6 mouse as controls previously submitted to GEO at number GSE101551 on the same time, same experiment.

first: Sandrine

last: LUCE

first: Sophie

last: GUINOISEAU

first: Alexis

last: GADAULT

last: LETOURNEUR

first: Patrick

last: NITSCHKE

first: Marc

last: BRAS

first: Michel

last: VIDAUD

first: Pierre

last: CHARNEAU

first: Etienne

last: LARGER

first: Maikel

last: COLLI

first: Décio

last: EIZIRIK

first: François

last: LEMONNIER

first: Christian

last: BOITARD


title: Combined control of the fibroblast contractile program by YAP and TAZ

status: Public on Jun 01 2021

city: Rochester

first: Daniel

middle: J.

last: Tschumperlin

state: MN

address: 200 First St SW, AL 4-184

department: Physiology and Biomedical Engineering

institute: Mayo Clinic

summary:
YAP and TAZ are transcription cofactors implicated in the contractile and pro-fibrotic activation of fibroblasts. Fibroblast contractile function is important in alveologenesis, as well as in lung wound healing and fibrosis. As paralogs, YAP and TAZ may have independent or redundant roles in regulating transcriptional programs and contractile function.
Using IMR-90 lung fibroblasts, microarray analysis and traction microscopy we tested whether independent YAP or TAZ knockdown alone was sufficient to limit transcriptional activation and contraction in vitro.

overall_design: IMR-90 cells were stimulated with TGFβ1 (2 ng/ml) for 72 hours in the presence of scrambled, YAP, TAZ or both YAP and TAZ siRNA (n=3 replicates per condition). Transcript levels were evaluated using the Affymetrix GeneChip PrimeView Human Gene Expression Array. Transcripts changed by more than 2-fold with a p-value<0.05 were analyzed using Ingenuity Pathway Analysis

last: Link

first: Kyoung

last: Choi

first: Ana

last: Diaz Espinosa

first: Dakota

last: Jones

first: Andrew

middle: J

last: Haak


title: Environmental Stressors Impact Placentation Through Actions On Trophoblast, Immune, and Endothelial Cell Dynamics

city: Kansas City

first: Khursheed

last: Iqbal

state: Kansas

address: 3901 Rainbow Blvd

department: Pathology

institute: University of Kansas Medical Center

summary: Our environment is replete with chemicals that can affect embryonic and extraembryonic development. Dioxins, such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD), are compounds affecting development through the aryl hydrocarbon receptor (AHR). TCDD exposures can lead to placental adaptations and at higher doses pregnancy termination. Deep intrauterine endovascular trophoblast cell invasion was a prominent placentation site adaptation to TCDD. TCDD-mediated placental adaptations were dependent upon maternal AHR signaling but not placental or fetal AHR nor the presence of a prominent AHR target, cytochrome P450 1A1 (CYP1A1). At the placentation site, TCDD stimulated CYP1A1 transcription within endothelial cells but not trophoblast cells. Immune and trophoblast cell behaviors at the uterine-placental interface were guided by the actions of TCDD on endothelial cells. In summary, we have identified an AHR regulatory pathway activated by environmental stressors affecting uterine and trophoblast cell dynamics and the formation of the hemochorial placenta.

overall_design: Pregnant rats treated with TCDD at gestational day (gd) 6.5, PBMCs collected at gd 13.5.

first: Michael

last: Soares


status: Public on Jun 04 2021

first: Nicolas

middle: Alejandro

last: Gort-Freitas

address: 200 Longwood Ave

department: Systems Biology

institute: Harvard Medical School

summary: Immunotherapy is revolutionizing cancer treatment, but is often restricted by toxicities. What distinguishes adverse events from concomitant antitumor reactions remains poorly understood. Here, using anti-CD40-treatment in mice as a model of Th1-promoting immunotherapy, we show liver macrophages’ vulnerability to promote local adverse events. Mechanistically, tissue-resident Kupffer cells mediate liver toxicity by sensing lymphocyte-derived IFN-g and producing IL-12. Conversely, dendritic cells are dispensable for toxicity but drive tumor control. Though macrophages, IL-12, and IFN-g are not necessarily toxic themselves, we find that they prompt a neutrophil response that determines the severity of tissue damage. We further show that similar inflammatory pathways characterize adverse events across tissues, following anti-PD-1 and anti-CTLA4 immunotherapies, and in humans. These findings implicate macrophages and neutrophils as mediators and effectors of aberrant inflammation in Th1-promoting immunotherapy, and suggest distinct mechanisms of toxicity and antitumor immunity.

overall_design: Single cell RNA sequencing (scRNAseq) of CD45-sorted and IL-12p40-EYFP-sorted cells from tumor and liver of IL-12p40-IRES-EYFP reporter mice that were treated or not with agonist anti-CD40 immunotherapy. CD45+ cells were sorted from untreated (n=2) and anti-CD40-treated (n=2) livers; IL-12p40-EYFP+ cells were sorted from anti-CD40-treated liver (n=2) and tumor (n=3).

first: Marie

last: Siwicki

middle: A

first: Marius

last: Messemaker

first: Camilla

last: Engblom

first: Rapolas

last: Zilionis

first: Allon

last: Klein

first: Mikael

last: Pittet


title: Self-reactivity shapes functional diversity of naive CD8+ T cells by co-opting tonic type I interferon [Array]

status: Public on Jun 19 2021

city: Hwasun-eup, Hwasun-gun

first: Jae-Ho

last: Cho

state: Jeollanam-do

address: 264, Seoyang-ro

institute: CHONNAM NATIONAL UNIVERSITY

summary: The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise role, functional relationship, and underlying mechanisms have not been elucidated completely. Here, we demonstrate that naive CD8+ T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon (T1IFN), resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+ cells. CD5hiLy6C+ cells differ from CD5loLy6C– and CD5hiLy6C– cells in their gene expression profiles and functional properties. Moreover, CD5hiLy6C+ cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such unique features of CD5hiLy6C+ cells are imprinted in a steady-state and observed even for those of monoclonal CD8+ T cell populations in a T1IFN dependent fashion. These findings demonstrate that self-reactivity shapes the functional diversity of naive CD8+ T cells by co-opting tonic T1IFN signaling.

overall_design: Gene profiles of 3 naive (CD44lo) CD8+ T cell subsets (CD5lo, CD5hi Ly6C-, and CD5hi Ly6C+)

first: Young-Jun

last: Ju

first: Sung-Woo

last: Lee


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis [RNA-Seq]

first: Argyris

last: Papantonis

summary: Mammalian chromosomes are three-dimensional entities shaped by converging and opposing forces acting on chromatin. Mitotic cell division induces drastic chromatin condensation, but following reentry into the G1 cell cycle phase, condensed chromosomes unwind to re-establish interphase organization. Here, we use a cell line allowing auxin-mediated degradation of RNA polymerase II to test its role in this transition. In situ Hi-C and super-resolution imaging showed that RNAPII is required for compartment and loop formation following mitosis. RNAPs also often counteract loop extrusion and, in their absence, longer and more prominent loops arise. Evidence from chromatin fractionation and in silico modeling attribute these effects to RNAPII-mediated cohesin loading at active promoters upon G1 reentry. Our findings reconcile the role of RNAPII in gene expression with that in chromatin architecture.

overall_design: Factory-seq protocol for enrichment of nascent RNA coupled with sequencing was applied to DLD1 and HCT116  cells

first: Nadine

last: Übelmesser

first: Natasa

last: Josipovic


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis [Cut&Tag-seq]

overall_design: Genome-wide binding profiles for the  CTCF, SMC1A and rad21 were investigated in DLD1 cells


title: Decreased  miR-4512 levels in monocytes and macrophages of individuals with systemic lupus erythematosus contribute to innate immune activation and neutrophil NETosis by targeting TLR4 and CXCL2.

city: Kunming, Yunnan, China

first: Danqi

last: Deng

address: 374 Dianmian Road, Wuhua District

institute: The Second Affiliated Hospital of Kunming Medical University

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Whole Transcriptome Sequencing Identifies Key circRNAs, lncRNAs and miRNAs Regulating Neurogenesis in Developing Mouse Retina

city: Wenzhou

first: Gang

last: Chen

address: 270 Xueyuan Road

institute: Eye Hospital of Wenzhou Medical University

summary: Retina is the fundamental unit of central nervous system, whose development is orchestrated by the intricate crosstalk of diverse RNA species. However, the molecular complexity of neural retina development remains poorly elucidated, limiting the therapy of retinal neurodegenerative diseases. Herein, we performed whole transcriptome sequencing of mouse retina in E14.5, P1, P7, P12, P17 and adult. The circRNA, lncRNA, miRNA and mRNA expression profiles of the developing retina were comprehensively characterized and the differentially expressed RNAs were screened.

overall_design: C57BL/6J mice were obtained from Vital River Laboratory (Beijing, China) and were kept in a pathogen-controlled environment in standard cages and were fed ad libitum. Retinas were dissected from mice in six developmental periods: embryonic day (E) 14.5, postnatal day (P) 1, 7, 12, 17 and adult. Total RNA was extracted by miRNA Kit (Omega Bio-tek) and three RNA libraries of small RNAs, long RNAs and circRNAs were constructed and whole-transcriptome sequencing was performed using developing retina of mice.

first: Zai-long

last: Chi


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis [ATAC-Seq]

overall_design: Assay for Transposase-Accessible Chromatin using sequencing in DLD1 cells


title: Decreased  miR-4512 levels in monocytes and macrophages of individuals with systemic lupus erythematosus contribute to innate immune activation and neutrophil NETosis  by targeting TLR4 and CXCL2 [RNA-seq]

summary: Peripheral blood mononuclear cells from SLE patients  (n = 5) and healthy controls  (n = 5) were used for miRNA–mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE.

overall_design: mRNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from patients with SLE (n=5) and healthy controls

first: Binbin

last: Yang


title: High-resolution transciptome mapping and N6-methyladenosine modification mapping of 3T3-L1 derived adipocytes

city: nanjing

first: Zhang

last: Jun

state: jiangsu

address: longmiandadao

institute: China Pharmaceutical University

summary:
Purpose:Detect transcriptome-wide mapping of m6A modifications by MeRIP-seq between Rhein and DMSO treated 3T3-L1 differentiation adipocytes at the preadipocytes, MCE stage and differentiation stage.
Methods:Total RNA was extracted using TRIzol Reagent followed by chemical fragmentation.  The fragmented RNA was incubated with anti-m6A antibody. The desired m6A-enriched RNA eluate was used to construct cDNA library in parallel with input control.
Conclusion: Our study revealed the difference of m6A-methylated RNA between DMSO and Rhein treated cells by RNA-seq and MeRIP-seq technologies.

overall_design: Compare the difference of m6A-methyalated RNA at the preadipocytes, MCE stage and differentiation stage during differentiation between DMSO and Rhein treated samples.

first: Linyuan

last: Huang

first: Jun

last: Zhang

first: Xue

last: Mi


title: Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus [RNA-Seq]

city: Chicago

first: Carole

last: Ober

state: IL

address: 920 E 58TH ST

department: Human Genetics

institute: The University of Chicago

summary: We generated genome-wide gene expression data (RNAseq) from cultured airway epithelial cells exposed to rhinovirus (RV) and a vehicle control (48 hour treatment). This data was generated in combination with genome-wide DNA methylation data (RNAseq) and genotypes from the same individuals.

overall_design: Identification of expression quantitative trait loci (meQTLs) in vehicle- and RV-treated airway epithelial cells, and colocalization with childhood onset and adult onset GWASs.

first: Marcus

last: Soliai

first: William

last: Wentworth-Sheilds


title: RNA polymerase II is necessary for spatial chromatin reorganization following exit from mitosis [ChIP-Seq]

city: Goettingen

address: Robert-Koch-Str 40

institute: University Medical Center Goettingen

overall_design: Genome-wide binding profiles for the non-histone DNA-binding proteins GFP tagged RNA Pol II, CTCF and SMC1a as well as histone modification H3K27ac were investigated in DLD1 cells


title: Impact of the SnRK1 protein kinase on sucrose homeostasis and the transcriptome during the diel cycle

city: Oeiras

first: Jingtao

last: Lilue

state: Lisbon

address: Rua da Quinta Grande, 6

department: Bioinformatics facility

country: Portugal

institute: Instituto Gulbenkian de Ciencia

summary:
Sucrose Non-Fermenting1-Related Kinase1 (SnRK1) is an evolutionarily conserved protein kinase with key functions in energy management during stress responses in plants.
To address a potential role of SnRK1 under non-stress conditions, we performed a metabolomic and transcriptomic characterization of 20 d-old rosettes of Arabidopsis SnRK1 gain- and loss-of-function mutants during the diurnal cycle.
SnRK1 manipulation altered the slope of the correlation between sucrose and trehalose 6-phosphate (Tre6P). It also modulated the flux of carbon to the tricarboxylic acid cycle downstream of Tre6P-signalling. SnRK1 depletion modified expression of SnRK1-induced genes least at the end of the day (when Tre6P levels peak) and most at the end of the night (when Tre6P levels are lowest). Expression of a subset of these genes was attenuated by inducible Tre6P accumulation in a time-of-day dependent manner. Finally, transcriptional profiling uncovered a wide impact of SnRK1 on gene expression in non-stress conditions, establishing a clear connection with iron and sulfur metabolism.
In conclusion, SnRK1 plays central functions in metabolic and transcriptional regulation in the absence of stress. SnRK1 is further involved in the reciprocal control of sucrose-driven Tre6P production and/or degradation and its activity is modulated by daily fluctuations in Tre6P levels.

overall_design: End of day (EoD) and end of night (EoN) 20 day-old Arabidopsis thaliana whole rosette samples from control (Col-0), SnRK1α1 overexpressor (SnRK1α1-OE), and SnRK1α partial loss-of-function sesquiα2 mutant (snrk1α1-/- ; snrk1α2+/-), grown under an equinoctial (12:12) photoperiod. Each condition is represented by 3 biological replicates.

first: Bruno

last: Peixoto

first: Thiago

last: Moraes

first: Virginie

last: Mengin

first: Leonor

last: Margalha

first: Rubén

last: Vicente

first: Regina

last: Feil

first: Melanie

last: Höehne

first: António

last: Sousa

first: Mark

last: Stitt

first: John

last: Lunn

first: Elena

last: Baena-González


title: Gene expression in Aim2 (B6) knockout mice or F1 littermate Aim2 wild type controls

city: Calgary

first: Daniel

last: Muruve

state: Alberta

address: 3280 Hospital Dr. NW

department: Medicine

country: Canada

institute: University of Calgary

summary: Comparative gene expression in Aim2 KO and WT controls.

overall_design: In this study, we treated 3 Aim2 KO mice and 3 Aim2 WT controls with nephrotoxic serum to induce anti-GBM glomerulonephritis. mRNA gene expression was analyzed at day 9. 3 untreated WT and KO mice were also analyzed for baseline.

first: Hyunjae

last: Chung


title: Pancreatic Differentiation of stem cells reveals pathogenesis of a syndrome of Ketosis-Prone Diabetes

city: Houston

first: Malgorzata

last: Borowiak

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: We describe an unusual course of Ketosis Prone Diabetes and investigate potential mechanisms using induced pluripotent stem cell technology with high throughput mRNA sequencing and validation of a lecuine sensitive mTOR pathway.

overall_design: Comparison of patient versus control iPS cells and differentiation to pancreatic progenitors with metabolomics and rna-sequencing

first: Ashok

last: Balasubramanyam

first: Sanjeet

last: Patel


title: High-throughput 3-prime end RNA-seq of Pseudomonas aeruginosa response to Azithromycin

city: Pittsburgh

first: Charles

middle: Joel

last: McManus

state: Pennsylvania

address: 4400 Fifth Ave

department: Biological Sciences

institute: Carnegie Mellon University

summary: P. aeruginosa produces serious chronic infections in hospitalized patients and immunocompromised individuals, including cystic fibrosis patients. The molecular mechanisms by which P. aeruginosa responds to antibiotics and other stresses to promote persistent infections may provide new avenues for therapeutic intervention. Azithromycin (AZM), an antibiotic frequently utilized in cystic fibrosis treatment, is thought to improve clinical outcomes through a number of mechanisms including impaired biofilm growth and quorum sensing in P. aeruginosa. However, the mechanisms underlying the transcriptional response to AZM remain unclear. Here, we interrogated the P. aeruginosa transcriptional response to AZM using a fast and affordable genome-wide approach to quantitate RNA 3-prime-ends (3pMap). We identify new riboregulators and identify a prominent role of transcription termination in the response to AZM treatment.

overall_design: Twelve total samples were analyzed with three replicats in each of four conditions: 1) planktonic culture, 2) biofilm culture, 3) planktonic + azithromycin, 4) biofilm + azithromycin

first: Salini

last: Konikkat

first: Michele

last: Scribner

first: Vaughn

last: Cooper


title: Transcriptomic analysis (RNA-seq) of BRCA1-proficient and BRCA1-deficient ovarian cancer cells treated with the triazene compound CT913 and its metabolite CT913-M1

status: Public on May 31 2021

city: Dresden

first: Konrad

last: Grützmann

address: Schubertstraße 15

department: Core Unit for Molecular Tumor Diagnostics

institute: National Center for Tumor Diseases partner site Dresden

summary: Extending the therapeutic spectrum of PARP-inhibition (PARPi) beyond HR-deficiency or reverting PARPi resistance is of high clinical interest. This is particularly true for the identification of innovative therapeutic strategies for ovarian cancer, given the recent advances in the use of PARPi in clinical practice. In this regard, the combination of PARPi with chemotherapy is a promising strategy for defining new therapeutic standards. In this study, we analysed the therapeutic effect of novel triazene derivatives, including the drug CT913 and its metabolite CT913-M1 on ovarian cancer cells and describe their interaction with PARPi. This is the first study analysing the potential therapeutic effect of these components. In vitro assays for drug characterization including RNA-seq were applied in a selected panel of ovarian cancer cell lines. CT913 treatment conferred a dose-dependent reduction of cell viability in a set of platinum-sensitive and platinum-resistant ovarian cancer cell lines with an IC50 in the micro- to almost millimolar range (107-940µM), whereas its metabolite CT913-M1 was about 10-fold more potent (IC50 of 17-93µM). Neither of the drugs increased the cytotoxic effect of cisplatin, CT913 might even antagonize it. Furthermore, CT913 conferred synthetic lethality in BRCA1-deficient ovarian cancer cells, indicating that homologues recombination (HR) repair may contribute to its mechanism of action. Importantly, CT913 sensitized for olaparib treatment, independently of BRCA-1 mutational status, supporting the finding that CT913 may act partially independent of an impaired HR. CT913 treatment led to changes in gene transcription. CT913 strongly induced CDKN1A transcription, suggesting cell cycle arrest as an early response to this drug. It also downregulated a variety of transcripts involved in prominent DNA-repair pathways, such as HR, mismatch repair (MMR) or nucleotide excision repair (NER). This is the first study, suggesting the triazene drug class CT913 as auxiliary drug for extending the therapeutic spectrum of PARPi.

overall_design: UWB1.289 or UWB1.289+BRCA1 ovarian cancer cells were treated with 1000µM CT913 or 40µM CT913-M1 or standard medium as control for 24h, followed by total RNA-extraction and RNA-seq. There are two replicates for each group, that is 12 samples in total.

first: Catharina

last: Wichmann

last: Klotz

first: Hans-Joachim

last: Zeiler

first: Ralf

last: Hilger

first: Alexander

last: Krüger

first: Pauline

last: Wimberger

first: Jan

middle: D

last: Kuhlmann


title: Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus [Methylation array]

first: Carole

last: Ober

summary: We generated genome-wide DNA methylation data from cultured airway epithelial cells exposed to rhinovirus (RV) and a vehicle control (48 hour treatment). This data was generated in combination with genome-wide expression data (RNAseq) and genotypes from the same individuals.

overall_design: Identification of DNA methylation quantitative trait loci (meQTLs) in vehicle- and RV-treated airway epithelial cells, and colocalization with childhood onset and adult onset GWASs.

first: Marcus

middle: M

last: Soliai

first: William

last: Wentworth-Sheilds


title: High-resolution transcriptome mapping and N6-methyladenosine modification mapping of 3T3-L1 derived adipocytes (RNA-Seq)

first: Zhang

last: Jun

first: Linyuan

last: Huang

first: Jun

last: Zhang

first: Xue

last: Mi


title: Decreased  miR-4512 levels in monocytes and macrophages of individuals with systemic lupus erythematosus contribute to innate immune activation and neutrophil NETosis  by targeting TLR4 and CXCL2 [miRNA-seq]

first: Danqi

last: Deng

summary: We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.

overall_design: miRNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from patients with SLE (n=5) and healthy controls

first: Binbin

last: Yang


title: RNA-mediated activity-based protein profiling reveals the substrates of a human dihydrouridine synthase

city: princeton

first: Ang

last: Li

state: NJ

address: Washington Road

department: chemistry

institute: princeton university

summary: We adapted the iCLIP method to map DUS3L-dependent DHU sites in a transcriptome-wide manner by treating the cells with 5-FUrd.

overall_design: Flp-In T-Rex 293 cells expressing 3xFlag-DUS3L were treated with 5-FUrd, DUS3L-RNA were extracted and subject for Iclip library preparation.

first: Ralph

last: Kleiner


title: Mutations on a novel brain-specific isoform of PGC1α leads to extensive upregulation of neurotransmitter-related genes and sexually dimorphic motor deficits in mice

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: We identified a new brain-specific isoform of PGC1 α that is the main isoform in neurons. Mutation of this gene leads to a sex dimorphic gene expression program in the female cerebellum and to alter motor coordination

overall_design: We utilized microarrays to establish the differential gene expression program in the cerebellum or rest of brain (whole brain minus cerebellum) in WT and mutant littermates; males and females were separately profiled.

first: Janine

middle: H

last: Santos


title: Transcriptomic profiling by RNA-seq of A. baumannii 17978 wild-type, and ∆A1S_1874 mutants.

status: Public on May 25 2021

city: Daegu

first: Md.

middle: Maidul

last: Islam

address: 680 Gukchaebosang-Ro, Jung-gu

department: Department of Microbiology

institute: Kyungpook National University

summary: Acinetobacter baumannii A1S_1874 gene encodes as a LysR-type transcriptional regulator. LysR family regulators known to regulate biofilm formation, antibiotic resistance, and the expression of diverse genes in other Gram-negative bacteria. However, A1S-1874 has never been characterized in Acinetobacter baumannii, and the studies about the regulon of A1S-1874 are not discovered. In this study we revealed that A1S_1874 differentially regulates at least 302 genes including the csu pilus operon, N-acylhomoserine lactone synthese gene, A1S_0112-A1S_0118 operon, type 1v secretion system related genes that are involved in biofilm formation, surface motility, adherence, quorum sensing and virulence. Overall, our data suggests that A1S-1874 is a key regulator of Acinetobacter baumannii biofilm formation and gene expression.

overall_design: RNA-seq of total RNA extractions from A. baumannii 17978 wild-type, ∆A1S_1874 mutants grown at 37 ºc upto an OD600=1.00

first: Md

first: Minsang

last: Shin


title: Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus

overall_design: Refer to individual Series


title: ATAC-seq data from murine peripheral T-cell lymphoma and control normal T cells, NKT cells and NK cells

status: Public on May 18 2021

city: Bron

first: Sylvain

last: Mareschal

address: Centre de Biopathologie Est, 59 boulevard Pinel

department: NGS-HCL platform

institute: Hospices Civils de Lyon

summary: Peripheral T-cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcome.T-cell receptor (TCR) is emerging as a key driver of T lymphocytes transformation. However, the role of chronic TCR activation in lymphomagenesis and in survival of lymphoma cells is still poorly understood. Using an original mouse model, we report here that chronic TCR stimulation drives T-cell lymphomagenesis whereas TCR signaling does not contribute to PTCL survival.  Epigenetic analyses of mouse PTCLs using ATAC-seq revealed a NK-like reprogramming of PTCL cells with increase accessibility to OCR associated with NK cells.

overall_design: 18 samples. 9 mPTCLs generated after transfer of p53KO T cells into syngeneic recipient C57BL/6 CD3KO mice, 3 normal T cells, 3 normal NKT cells and 3 normal NK cells

last: Carras

first: Amel

last: Chebel

first: Emmanuel

last: Bachy

first: Laurent

last: Genestier


title: Gene expression profiles of human Treg and Tconv cells induced by signals of pseudostarvation

status: Public on May 17 2021

city: Napoli

first: Paola

last: De Candia

address: via Pansini 5

country: Italy

institute: UNIVERSITA' DEGLI STUDI DI NAPOLI FEDERICO II - Dipartimento di Medicina molecolare e Biotecnologie mediche

summary: We have employed whole genome microarray expression profiling of human Treg and Tconv cells as a discovery platform to identify genes differentially expressed upon signal of pseudostarvation (either mTOR inhibition or leptin neutralizaion) responsible for proliferation of Treg cell on one side and inhibition of Tconv cells on the other. Human Treg and Tconv cells isolated from healthy donors were pretreated or not with rapamycin or leptin mAb and stimulated with anti-CD3 and anti-CD28 beads for 12h.

overall_design:
Gene expression was evaluated in human freshly isolated Treg and Tconv cells, and in the same cells after 1 hour rapamycin pretreatment or leptin mAb-treatment and compared to vehicle-pretreated cells, upon 12 hours stimulation with anti-CD3/CD28 beads, in order to define the effect of signals of pseudo-starvation on human Treg/Tconv cells. Three independent experiments were performed for each of the different experimental conditions using different donors for each experiment.

Three channel array hybridization. Analyzed as single-channel.

first: Claudio

last: Procaccini

last: de Candia

first: Dario

last: Di Silvestre

last: Greco

first: Giuseppe

last: Matarese


title: Spleen RNA-seq from 20181203 Mouse 7d IL-33 Experiment with Wild Type (WT) and IL13-/- mice

city: Cambridge

first: Melvin

last: Zhang

address: 1 Portland St.

department: Inflammation & Immunology

institute: Pfizer

summary: The purpose of this study is to evaluate gene expression differences between spleens of WT and IL13-/- mice treated with either IL-33 or PBS vehicle. In addition, RNA-seq will allow us to clearly decipher the isoforms of ST2 transcript.

overall_design: RNA-seq analysis of spleens of 3- to 4-month-old WT and IL13-/- mice.

first: Arun

last: Shipstone

first: Angela

last: Hadjipanayis

first: Marion

last: Kasaian


title: Single-cell transcriptomics of peripheral blood reveals a novel B-cell subset in renal allograft recipients with accommodation

city: Changsha

first: 皓

last: 李

state: China

address: Changsha Organ Transplantation Center, Third Xiangya Hospital, Changsha, Hunan，China

institute: the third Xiangya hospital

summary: Kidney transplantation is a preeminent treatment for end-stage renal disease . The application of immunosuppressants is needed for kidney recipients to avoid allograft rejection but increase the risk of infection, and balance between rejection and infection is an important in clinical to reach the immune accommodation. Here, we use single-cell RNA sequencing to fully assess the immune status of peripheral mononuclear cells in kidney recipients. and compared the differences between kidney recipients and healthy people to describe the characteristics of the immune accommodation of kidney recipients. We found a novel B cell subset (CD19+IGKC+IGLC3lowTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of healthy people and verified by flow cytometry. which may have potential regulatory potential. Furthermore, we found that IL32 may increase the expression of CD19+IGKC+IGLC3lowTCL1A-CD127+ Bcells. In summary, we found that the CD19+IGKC+IGLC3lowTCL1A-CD127+B subgroup with immunomodulatory potential is inhibited in kidney recipients with accommodation state, and IL-32 has therapeutic potential for this.

overall_design:
Sc-RNA-seq for PBMC from kidney recipients, patient with end stage renal disease and healthy control.
3 sample:
title; source name; tissue; age; gender
KTx; kidney recipient; blood; 32; male
HC; healthy control; blood; 30; male
ESRD; end-stage renal disease; blood; 35; male

first: Yingzi

last: Ming

first: Quan

last: Zhuang

first: Hao

last: Li


title: RNA-seq of KIR3DL3+ and KIR3DL3- CD8 terminally differentiated effect memory T cells (TEMRA)

status: Public on May 27 2021

city: Bronx

first: Yao

last: Wei

state: New York

address: 1300 Morris Park Ave F411

institute: Albert Einstein college of medicine

summary: The majority (60-97%) of KIR3DL3+ CD8 T cells belongs to TEMRA. To understand the function and characteristic of KIR3DL3+ CD8 T cells, we performed RNA-seq of KIR3DL3+ and KIR3DL3- CD8 TEMRA cells

overall_design: CD8 T cells were enriched from fresh PBMCs by CD8 microbeads. 10,000 to 20,000 KIR3DL3+ and KIR3DL3- CD8 TEMRA, defined as CD3+CD8+CD45RA+CCR7- were sorted by the BD FACSAria for RNA-seq.

first: Xingxing

last: Zang

first: Phillip

last: Galbo

first: Deyou

last: Zheng


title: Gene architecture directs splicing outcome in separate nuclear spatial regions

status: Public on May 14 2021

city: Tel Aviv

first: Gil

last: Ast

state: Israel

address: Haim Levanon 55

country: Israel

institute: Tel Aviv University

summary: How the splicing machinery defines exons or introns as the spliced unit has remained a puzzle for 30 years. Here we demonstrate that peripheral and central regions of the nucleus harbor genes with two distinct exon-intron GC content architectures that differ in the splicing outcome. Genes with low GC content exons, flanked by long introns with lower GC content, are localized in the periphery, and the exons are defined as the spliced unit. Alternative splicing of these genes results in exon skipping. In contrast, the nuclear center contains genes with a high GC content in the exons and short flanking introns. Most splicing of these genes occurs via intron definition, and aberrant splicing leads to intron retention. We demonstrate that the nuclear periphery and center generate different environments for the regulation of alternative splicing, and that two sets of splicing factors form discrete regulatory subnetworks for the two gene architectures. Our study connects 3D genome organization and splicing, thus demonstrating that exon and intron definition modes of splicing occur in different nuclear regions.

overall_design: Examination of Lamin A/C distribution in order to map topologically associated domains (TADs)  in the nucleus. This was done in two cell lines - K562 and GM12878.


title: Gene expression signatures in oridonin-treated WT and R878H hematopoietic stem cells

status: Public on May 13 2021

city: Tianjin

first: Jianwei

last: Wang

address: 10 Yuexin Street, Binhai New Area

institute: HAIHE LABORATORY OF CELL ECOSYSTEM

summary: Analysis of WT-Ctl v.s. WT-Ori and R878H-Ctl v.s. R878H-Ori hematopoietic stem cell (lineage-, c-kit+ Sca-1+ CD150+, CD34-). The four population of hematopoietic stem cell (HSC) were purified from the bone marrow of WT and R878H recipent mice treated with vehicle or oridonin. Results provide insight into the role of oridonin in R878H HSC.

overall_design: WT-Ctl, WT-Ori, R878H-Ctl and R878H-Ori HSCs from the bone marrow of recipient mice, then subjected into deep sequencing, in triplicate, using Illumina HiSeq platform.


title: TCR repertoire analysis revealed the highly conserved TCR repertoire in the bilateral tumor in mice

status: Public on May 12 2021

city: Noda City Chiba

first: Mikiya

last: Tsunoda

address: 2669 Yamazaki

department: Research Institute for Biomedical Sciences

country: Japan

institute: Tokyo university of science

summary: Temporal analysis of T-cell receptor (TCR) repertoire has been used to monitor treatment-induced changes in antigen-specific T cells in patients with cancer. However, lack of experimental model that allows the temporal analysis of TCR repertoire in same individual in homogeneous population limit the understanding of causal relationship between changes in TCR repertoire and antitumor responses. A bilateral tumor model, in which tumor cells were inoculated into the bilateral backs of mice, can be used for temporal analysis in TCR repertoire. In this study, we examined the prerequisite for this strategy: TCR repertoire are conserved between the bilateral tumor with same growth rate. The bilateral tumors with equivalent tumor size and draining lymph nodes (dLN) were collected 13 days after the tumor inoculation to analyze the TCR repertoire of CD4+ and CD8+ T cells. Most of the tumor-infiltrating T-cell clones were highly conserved between the bilateral tumors, and the extent of clonal expansion was equivalent. In addition, the similarity between bilateral tumors were equivalent to the heterogeneity in one side of the tumor. The similarity of TCR repertoire in the bilateral dLN was markedly lower than that of the tumor, suggesting that tumor-reactive T-cell clones induced independently in each dLN were integrated during recirculation and then infiltrated the tumor. These findings suggest that our bilateral tumor model is suitable for temporal monitoring of TCR repertoire to evaluate temporal and treatment-induced changes in tumor-reactive T-cell clones.

overall_design: Lewis lung carcinoma (LLC) cells (5 × 105 cells /mouse) were inoculated subcutaneously (s.c.) into the bilateral backs of C57BL/6 mice (n=4). On day13, mice were sacrificed and the tumors and tumor-draining lymph nodes (DLN) were collected from the left and the right side. Tumor was devided into two pieces, and the TCR repertoire of CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in each piece were analyzed independently. Moreover, TCR repertoire of CD4+CD44hi and CD8+CD44hi T cells in the dLN were also analyzed.

first: Hiroyasu

last: Aoki

first: Haruka

last: Shimizu

first: Shigeyuki

last: Shichino

first: Kouji

last: Matsushima

first: Satoshi

last: Ueha


title: STING mediates immune responses in a unicellular choanoflagellate

city: Dallas

first: Arielle

last: Woznica

state: Texas

address: 6000 Harry Hines Blvd., NL4.110M

institute: UT Southwestern

summary: To reconstruct the ancestry of animal innate immunity, we have developed the choanoflagellate Monosiga brevicollis, one of the closest living relatives of animals, as a model for studying mechanisms underlying pathogen recognition and immune response. We found that M. brevicollis is killed by exposure to Pseudomonas aeruginosa bacteria and selectively avoids ingesting them. Moreover, M. brevicollis expresses STING, which, in animals, activates innate immune pathways in response to cyclic dinucleotides during pathogen sensing. M. brevicollis STING increases the susceptibility of M. brevicollis to P. aeruginosa-induced cell death and is required for responding to the cyclic dinucleotide 2’3’ cGAMP. Furthermore, similar to animals, autophagic signaling in M. brevicollis is induced by 2’3’ cGAMP in a STING-dependent manner.

overall_design: Examined the response of Monosiga brevicollis to different bacteria (Flavobacterium and P. aeruginosa) and cyclic dinucleotides (2'3' cGAMP and 3'3' cGAMP)


title: Promoter Capture Hi-C performed on A549 cells in a SARS-CoV2 infection timecourse

status: Public on May 10 2021

city: London

first: Mikhail

last: Spivakov

address: Du Cane Road

institute: MRC London Institute of Medical Sciences

summary: Here, A549 cells expressing the ACE2 receptor were infected with SARS-CoV2, and pCHi-C was performed at 0 (mock), 8 and 24 hours post-infection. This repository provides the raw pCHi-C sequence reads and downstream processed CHiCAGO data (Rds files).

overall_design:
A549 cells were crosslinked for promoter capture Hi-C (pCHi-C) experiments at zero (mock), eight and twenty-four hours post-infection with the SARS-Cov2 virus. pCHi-C libraries were generated and sequenced using paired-end NGS.
This data accompanies the publication "Topoisomerase 1 inhibition therapy protects against SARS-CoV-2- induced inflammation and death in animal models".

first: Helen

last: Ray-Jones

first: Valeriya

last: Malysheva

first: Michiel

last: Thiecke


title: Parental exposure to environmental stress results in evolutionarily conserved intergenerational changes in offspring gene expression

status: Public on May 07 2021

city: cambridge

first: Jonathan

middle: Lewis

last: Price

address: The Sanger Building Tennis Court Road

department: Biochemistry

institute: University of Cambridge

summary: These data demonstrate that parental exposure to bacterial infection and osmotic stress intergenerational changes in offspring gene expression in C. elegans, C. kamaaina, C. briggsae and C. tropicalis. Many of these intergenerational changes in gene expression are observed in multiple species and this data identified >250 genes that exhibit intergenerational changes in expression in all species tested.

sample_organism:
Caenorhabditis briggsae
Caenorhabditis elegans
Caenorhabditis kamaaina
Caenorhabditis tropicalis

overall_design: We exposed parents to multiple different bacterial pathogens (P. vranovensis, P. sp 15C5, Aeromonas sp. BIGb0469, and S. plymuthica) and osmotic stress and assayed effects on F1 and F3 gene expression.

first: Nick

last: Burton

first: Jon

first: Fabian

last: Braukmann

first: Eric

last: Miska


title: RNA-seq to determine the effect of EGCG on gene expression during WAT and BAT preadipocyte differentiation

status: Public on May 03 2021

city: Xinyang

first: pengpeng

last: Zhang

address: No.237 Nanhu Road Shihe District

institute: Xinayang Normal University

summary: The aims of the current study were to characterize the effects of EGCG on mRNA transcriptome during WAT and BAT adipocytes adipogenesis.

overall_design: Primary WAT and BAT preadipocyte were isolated, and induced to adipogenic differentiation in the presence or absence of EGCG. The samples were collected on Day 4 and day 8 post differentiation

first: Pengpeng

first: Yongjie

last: Xu

first: Haixia

first: Cencen

last: Li


title: Impact of sickle cell trait hemoglobin on the intraerythrocytic transcriptional program of Plasmodium falciparum

status: Public on May 26 2021

city: Durham

first: Steve

last: Taylor

address: 303 Research Dr

department: Division of Infectious Diseases

institute: Duke University School of Medicine

summary:
Purpose: The goals of this study are to compare parasite transcriptomes in sickle cell trait infected red blood cells during the intraerythrocytic developmental cycle (IDC) from in vitro time series and in vivo blood samples to identify new therapeutic targets in the treatment of malaria

Methods: In vitro time series: Parasites were synchronized to early ring-stage parasites and sampled every three hours for 48 hours to capture every stage of the IDC,  generating 16 RNA-seq libraries per replicate (128 total). In vivo blood samples: Samples were collected in an observational study of malaria in children in Kenieroba, Mali (ClinicalTrials.gov Identifier: NCT02645604). From children presenting with uncomplicated falciparum malaria, we selected all available samples from children with HbAS and matched each of these to a sample from a child with HbAA on: month of episode, parasite density, ethnic background, and, if possible, ABO blood type.

overall_design:
mRNA profiles of P. falciparum in HbAS iRBCs compared to HbAA
in vitro
  3 hour time points
  16 time points per replicate
  8 replicates (4 HbAA, 4 HbAS)
--------------------------------------
  128 RNA-seq libraries

in vivo
  16 HbAA
  16 HbAS
-------------------------
  32 RNA-seq libraries

first: Joseph

middle: W

last: Saelens

first: Jens

middle: E

last: Petersen

first: Elizabeth

last: Freedman

first: Robert

last: Moseley

first: Drissa

last: Konaté

first: Seidina

last: Diakité

first: Karim

last: Traoré

first: Natalie

last: Vance

first: Rick

last: Fairhurst

first: Mahamdou

last: Diakite

first: Steven

middle: B

last: Haase


title: RNA Sequencing Data-driven Dissection of Human Plasma Cell Differentiation Reveals New Potential Transcription Regulators

status: Public on Apr 30 2021

city: Montpellier

first: Jerome

last: Moreaux

address: 80 Av. Augustin Fliche

department: Biological Hematology

institute: CHRU Montpellier

summary: Plasma cells play an important role in the adaptive immune system through a continuous production of antibodies. Several hematological disorders result from the malignant transformation of antibody-secreting plasma cells. A clear understanding of the molecular processes underlying human plasma cell differentiation (PCD) will provide greater insight into such pathologies. Here we present a comprehensive, temporal program of gene expression data encompassing human PCD from memory B cells, using RNA sequencing. Our results reveal 6,374 differentially expressed genes classified into four temporal gene expression patterns. A stringent pathway enrichment analysis of these gene clusters highlights known pathways but also pathways largely unknown in PCD, including the heme biosynthesis and the glutathione conjugation pathways. Additionally, our analysis revealed numerous novel transcriptional regulators and helicases with consistent  stage-specific overexpression and potential importance in PCD, including BATF2, BHLHA15/MIST1, EZH2, WHSC1/MMSET and BLM. We have experimentally validated, for the first time, a role for BLM in regulating cell survival and proliferation during human PCD. Taken together, this RNA-seq analysis of PCD temporal stages helped identify co-expressed gene modules with associated up- /down- regulated transcription regulator genes that could represent major regulatory nodes for human plasma cell differentiation. These data constitute a unique resource of human PCD gene expression programs in support of future studies for understanding the underlying mechanisms that control PCD.

overall_design: Global RNA expression profiling was carried out for in vitro human plasma cell differentiation cell subpopulations, including memory B cells, preplasmablasts, plasmablasts and plasma cells.

first: Alboukadel

last: Kassambara

first: Laurie

last: Herviou

first: Michel

last: Jourdan

first: Coraline

last: Thibaut

first: Veronika

last: Vikova

first: Philippe

last: Pasero

first: Olivier

last: Elemento

first: Jérôme


title: Next Generation Sequencing Quantitative Analysis of soybean seeds Transcriptomes

status: Public on May 01 2021

city: Beijing

first: Wei

last: Wei

state: Beijing

address: Chaoyang District, Beichen West Road, Campus #1, No 2

institute: Institute of Genetics and Developmental Biology

summary: To investigate the regulatory mechanisms of GmNFYA in salt stress, leaves and roots of transgenic plants and JACK plants were collected for RNA extraction and sequencing. Clean reads of RNA-sequencing were mapped to soybean genome and genes that had a 2 fold increase or 50% decrease, compared to JACK, were defined as differential expressed genes (DEGs).

overall_design: mRNA profiles of soybean leaf and roots. Wild type (Jack) and GmNFYA overexpressing soybean.


title: Changes in Expressions of Spermatogenic Marker Genes and Spermatogenic Cell Population Caused by Stress

city: shijiazhuang

first: Pengxiang

last: Tian

state: hebei

address: 215 heping west road

institute: The second hospital of hebei medical university

summary:
Purpose: Many young adults are in a state of stress due to social and psychological pressures, which may result in male reproductive dysfunction. To provide new insight into this phenomenon, we investigated the relationship between pathological changes in rat spermatogenic cells and the expression of genes specific to spermatogenic cell types under different stress conditions.
Methods: After establishing rat stress models of different time durations, we observed pathological changes in testicular tissues through haematoxylin and eosin staining, and analysed gene expression in spermatogenic cells by RNA-seq, bioinformatic analysis, and reverse transcription qPCR (RT-qPCR).Three testicular samples were taken from each group to construct 12 cDNA libraries. For each sample, 3 μg RNA was used as the starting material. Ribosomal RNA was removed using the Epicentre Ribo-Zero™ Gold kit (Rat) (Epicentre, an Illumina company, Madison, WI, USA).
Results:Compared with the control group, there were 1,194 DEGs in the 3-day RS+IS group , including 455 upregulated genes and 739 downregulated genes , 1,774 DEGs in the 14-day RS+IS group including 1,124 upregulated genes and 650 downregulated genes, and 2,267 DEGs in the 21-day RS+IS group  including 1,366 upregulated genes and 901 downregulated genes. Mean-while, some same expression patterns were observed in three phenotypes.After comparison with single-cell sequencing data, 349 DEGs of spermatogenic cells at different developmental stages were found.
Conclusions:  Our study suggest that chronic psychosomatic stress can affect the spermatogenic transcriptome of the testes, leading to a significant change in the expression of the spermatogenic genes. At the same time, histopathological and immunohistochemical results showed that chronic stress may lead to pathological changes in spermatogenic cells and to a significant decrease in key regulatory proteins

overall_design: Testis transcriptome profiles of adult wild type (WT) and RS+IS rats were generated by RNA sequencing

first: P

first: G

last: Hao


title: Distinct B cell repertoires characterize patients with mild and severe COVID-19

status: Public on Apr 26 2021

city: New York

first: Yongchao

last: Ge

state: NY

address: One Gustave L Levy Place #1137

department: Neurology

institute: Icahn School of Medicine at Mount Sinai

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Distinct B cell repertoires characterize patients with mild and severe COVID-19 [VDJ]

summary: Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2 binding plasma cells and memory B cells after infection or vaccination. Previous work has shown evidence that germinal center reactions, a critical component of the B cell response, are disrupted in severe COVID-19. This may adversely affect protective immunity from re-infection. Consistent with an extrafollicular B cell response, severe COVID-19 patients have large scale changes in B cell populations such as elevated frequencies of clonally expanded, class switched, unmutated plasmablasts. However, it is not clear whether mild or asymptomatically infected individuals show similar differences in B cell repertoires. Here, we use single cell RNA sequencing of B cells to show that, in contrast to hospitalized COVID-19 patients, mildly symptomatic COVID-19 subjects have B cell repertoires skewed towards clonally diverse, somatically hypermutated memory B cells approximately 30 days after the onset of symptoms. This provides evidence that B cell responses are less disrupted in mild COVID-19, and that the infection resolves with the production of memory B cells.

overall_design: Characterization of B cell response in mild symptomatic COVID-19 patients

first: Kenneth

last: Hoehn

first: Palaniappan

last: Ramanathan

first: Stuart

last: Sealfon

first: Alexander

last: Bukreyev

last: Kleinstein


title: Comparative RNA-seq of P. yoelii WT vs pynot1-g null parasites in schizont and gametocyte stages

status: Public on May 24 2021

city: University Park

first: Scott

middle: E.

last: Lindner

address: W224 Millennium Science Complex

department: Biochemistry and Molecular Biology

institute: Penn State University

summary: In order to assess what PyNOT1-G contributes to Plasmodium gametocyte commitment and maturation, we conducted comparative RNA-seq on enriched schizonts and gametocytes. We identified many transcripts that are dysregulated in accordance with the gene deletion phenotype.

overall_design: Three biological replicates were conducted per parasite type, each with a control parasite line done in parallel.

first: Kevin

last: Hart

first: Aswathy

last: Sebastian

first: Istvan

last: Albert


title: Seasonal Heat Stress Effects on Transcriptomic Profiles and DNA Methylation of Bovine Oocytes

status: Public on Apr 27 2021

city: Gainesville

first: Zongliang

last: Jiang

state: FL

address: 2033 Mowry Rd

department: Animal Sciences

institute: University of Florida

summary: Heat stress affects oocyte developmental competence and is a major cause of reduced fertility in heat stressed cattle. Negative effects of heat stress on the oocyte have been observed at morphological, biochemical and developmental levels. However, the mechanisms by which heat stress affects the oocyte at the transcriptional and epigenetic levels remain to be further elucidated. Here we aimed to investigate the effect of heat stress on oocyte quality, transcriptomic profiles and DNA methylation of oocytes collected through the transition from spring to summer under Louisiana conditions. Summer heat resulted in a lower number of high quality oocytes obtained compared to the spring season. There was no difference in maturation rates of oocytes collected during spring as compared to summer. RNA sequencing analysis showed that a total of 212 and 93 genes were differentially expressed as a result of heat stress at the GV and MII oocytes, respectively. Five common genes (E2F8, GATAD2B, BHLHE41, FBXO44, and RAB39B) were significantly affected by heat in both GV and MII oocytes. A number of pathways were also influenced by heat stress including glucocorticoid biosynthesis, apoptosis signaling, and HIPPO signaling in GV oocytes, and Oct4 pluripotency, Wnt/beta-catenin signaling, and melatonin degradation I in MII oocytes, respectively. In addition, fluorescent immunocytochemistry analysis showed no difference in global levels of DNA methylation and DNA hydroxymethylation at either the GV or MII stage between spring and summer oocytes. The results of this study contribute to a better understanding of the effect of heat stress on the molecular mechanisms altered in bovine oocytes.

overall_design: Individual oocytes were collected monthly during spring (May) or Summer (July) from 6 cows (n=6). GV or MII oocytes were then pooled into groups of 4 for RNA-seq analysis.

first: Fabian

last: Diaz


title: Distinct B cell repertoires characterize patients with mild and severe COVID-19 [GEX]

first: Steven